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Mitogen activated protein kinase inhibition by PD98059 blocks nerve growth factor stimulated axonal outgrowth from adult mouse dorsal root ganglia in vitro

Sjögreen, B. LU ; Wiklund, P. LU and Ekström, Per LU (2000) In Neuroscience 100(2). p.407-416
Abstract

Nerve growth factor stimulated axonal outgrowth from explanted mouse dorsal root ganglia is dependent on mitogen activated protein kinase. PD98059 ([2-(2'amino-3'-methoxyphenyl)-oxanaphthalen-4-one]) blocks mitogen activated protein kinase by inhibiting its immediate upstream activator, mitogen activated protein kinase kinase (also known as MEK). Here we used PD98059 to study the role of mitogen activated protein kinase in the axonal outgrowth of adult dorsal root ganglia explants. Whereas PD98059 at 50μM left spontaneous axonal outgrowth unaffected, it markedly inhibited nerve growth factor stimulated axon growth when assessed after two days in culture. A mitogen activated protein kinase assay and immunoblotting using antibodies... (More)

Nerve growth factor stimulated axonal outgrowth from explanted mouse dorsal root ganglia is dependent on mitogen activated protein kinase. PD98059 ([2-(2'amino-3'-methoxyphenyl)-oxanaphthalen-4-one]) blocks mitogen activated protein kinase by inhibiting its immediate upstream activator, mitogen activated protein kinase kinase (also known as MEK). Here we used PD98059 to study the role of mitogen activated protein kinase in the axonal outgrowth of adult dorsal root ganglia explants. Whereas PD98059 at 50μM left spontaneous axonal outgrowth unaffected, it markedly inhibited nerve growth factor stimulated axon growth when assessed after two days in culture. A mitogen activated protein kinase assay and immunoblotting using antibodies discriminating between activated and inactivated kinase, both confirmed that PD98059 reduced the amount of activated enzyme in nerve growth factor stimulated preparations, while the total amounts of the kinase remained unchanged. Immunohistochemistry revealed the presence of neuronal mitogen activated protein kinase kinase and mitogen activated protein kinase itself. The latter enzyme was found to be activated in the growing axons, as seen by whole-mount labelling. At the ganglionic level activated mitogen activated protein kinase was preferentially detected in satellite cells.The results show that nerve growth factor stimulated axonal outgrowth in vitro from adult mouse dorsal root ganglia utilizes the mitogen activated protein kinase pathway. Copyright (C) 2000 IBRO.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Axons, MEK, NGF, Regeneration, Satellite cells
in
Neuroscience
volume
100
issue
2
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:0342472151
ISSN
0306-4522
DOI
10.1016/S0306-4522(00)00278-5
language
English
LU publication?
yes
id
ec41849a-c9fa-4e6c-b973-9dc28608d817
date added to LUP
2016-12-07 14:54:45
date last changed
2017-01-26 17:17:49
@article{ec41849a-c9fa-4e6c-b973-9dc28608d817,
  abstract     = {<p>Nerve growth factor stimulated axonal outgrowth from explanted mouse dorsal root ganglia is dependent on mitogen activated protein kinase. PD98059 ([2-(2'amino-3'-methoxyphenyl)-oxanaphthalen-4-one]) blocks mitogen activated protein kinase by inhibiting its immediate upstream activator, mitogen activated protein kinase kinase (also known as MEK). Here we used PD98059 to study the role of mitogen activated protein kinase in the axonal outgrowth of adult dorsal root ganglia explants. Whereas PD98059 at 50μM left spontaneous axonal outgrowth unaffected, it markedly inhibited nerve growth factor stimulated axon growth when assessed after two days in culture. A mitogen activated protein kinase assay and immunoblotting using antibodies discriminating between activated and inactivated kinase, both confirmed that PD98059 reduced the amount of activated enzyme in nerve growth factor stimulated preparations, while the total amounts of the kinase remained unchanged. Immunohistochemistry revealed the presence of neuronal mitogen activated protein kinase kinase and mitogen activated protein kinase itself. The latter enzyme was found to be activated in the growing axons, as seen by whole-mount labelling. At the ganglionic level activated mitogen activated protein kinase was preferentially detected in satellite cells.The results show that nerve growth factor stimulated axonal outgrowth in vitro from adult mouse dorsal root ganglia utilizes the mitogen activated protein kinase pathway. Copyright (C) 2000 IBRO.</p>},
  author       = {Sjögreen, B. and Wiklund, P. and Ekström, Per},
  issn         = {0306-4522},
  keyword      = {Axons,MEK,NGF,Regeneration,Satellite cells},
  language     = {eng},
  month        = {09},
  number       = {2},
  pages        = {407--416},
  publisher    = {Elsevier},
  series       = {Neuroscience},
  title        = {Mitogen activated protein kinase inhibition by PD98059 blocks nerve growth factor stimulated axonal outgrowth from adult mouse dorsal root ganglia in vitro},
  url          = {http://dx.doi.org/10.1016/S0306-4522(00)00278-5},
  volume       = {100},
  year         = {2000},
}